Research Summary

Small molecule modulators of autophagy and autophagy related pathways

Every cell in our body is equipped with housecleaning machinery. This machinery called autophagy is universally present in all cells from yeast to humans. During nutrient starvation, autophagic processes promote cell survival by recycling superfluous cytoplasmic proteins and organelles. On the other hand, several intracellular pathogens including bacteria (Salmonella, Shigella, Mycobacterium, Group A Streptococcus, etc.) and viruses (herpes simplex virus, HIV, etc.) subvert autophagy to prevent their elimination by degradation in host lysosomal compartments. Autophagy also serves a neuroprotective role, as it clears large aggregates of mutant polyubiquitylated proteins resistant to proteasomal degradation. Furthermore, apart from neurodegenerative and infectious diseases, autophagy has been shown to be involved in heart diseases, atherosclerosis, certain myopathies, innate and adaptive immune responses, Crohn's disease and cancer. Thus targeting autophagy is a potentially exciting avenue that is just beginning to be exploited for disease and cancer therapeutics.

Autophagic mechanisms were elucidated in yeast which remains the best understood system. I intend to use autophagy in yeast as a model to screen for potential drug candidates that would be tested in mammalian cells for their efficacies to prevent propagation of intracellular pathogens and cancer cells. Further insights about the mode of action of these molecules will lead to a better understanding of this important process and yield potential therapeutic agents.